Haplotype and linkage disequilibrium of TP53-WRAP53 locus in Iranian-Azeri women with breast cancer

Abstract

Among the cancer susceptibility genes, TP53 is one of the crucial genes involved in cell cycle regulations and, therefore, it greatly affects breast cancer initiation and progression. In addition, WRAP53 —a natural antisense transcript—regulates TP53 transcription and, as a protein, modulates the normal cell cycle, which results in breast cancer susceptibility. In this study, we aimed to analyze a haplotype comprising four SNPs, including rs1042522, rs17878362, rs2287499, and rs2287498, which are located at 5′ regions of the TP53 and WRAP53 genes, in 118 patients and 110 healthy controls of the Iranian-Azeri population. In silico studies were conducted using the SIFT, Polyphen2, Fanthmm, RNAsnp, and SNP&GO online servers. Linkage disequilibrium (LD) and D′ for each combination of the markers were calculated via the Haploview program. Our results showed that the GA 1 CC haplotype was the most frequent in the studied population. Additionally, no significant LD between any pairwise haplotypes was observed. The GA 1 CC and CA 2 GC haplotypes were significantly associated with breast cancer susceptibility. Moreover, the in silico analysis revealed the negative effects of rs2287499 and rs1042522 on WRAP53 and P53, respectively. In conclusion, the CA 1 GC haplotype was strongly identified as a breast cancer risk factor, and the GA 1 CC haplotype was assumed to be a protective factor against breast cancer risk. Hence, these markers may potentially be used as molecular prognostic and predictive biomarkers for breast cancer.

Nuclear WRAP53 promotes neuronal survival and functional recovery after stroke

“…In this context, the common nonsynonymous SNP in codon 68 of the first coding exon of Wrap53 (rs2287499 c.202C>G) results in the amino acid change arginine (Arg 68 ) to glycine (Gly 68 ), which might affect protein function (33). In particular, the Wrap53 C>G SNP has been associated with primary tumor risk (33)(34)(35)(36)(37). However, the impact of this SNP on stroke remains unexplored.…”

Haplotypes of single cancer driver genes and their local ancestry in a highly admixed long-lived population of Northeast Brazil

“…, 2019 ; Zhang et al , 2019 ; Ozola et al. , 2019 ; Pouladi et al , 2019 ; Elshazli et al. , 2020 ; Kamiza et al, 2020 ; Liu et al , 2020 ) CTG (15.0%) 1 28.29 0.258 0.93-1.0 ACG (14.6%) -0.97 25.27 0.258 0.89-1.0 ATG (11.0%) -0.95 72.4 0.606 0.9-0.98 HNF1B CGG (49.3%) rs7501939 rs11651052 rs11658063 -0.95 72.4 0.606 0.9-0.98 rs7501939 ( Setiawan et al , 2012 ; Chornokur, 2013a ; Nikolić et al, 2014 ; Kristiansen et al.…”

Differential Effects of WRAP53 Transcript Variants on the Biological Behaviours of Human Non-Small Cell Lung Cancer Cells

“…The signi cance of WRAP53β in tissue homeostasis is demonstrated by the nding that inherited mutations in WRAP53β lead to telomere dysfunction and dyskeratosis congenita, increasing the risk of tumorigenesis [22]. Moreover, single nucleotide polymorphisms and downregulation of WRAP53β are associated with various sporadic forms of cancer, including breast and ovarian cancer [23][24][25][26]. In addition, WRAP53β downregulation is correlated with resistance of head and neck cancer to radiotherapy [27], as well as disruption of the DNA damage response in ovarian tumours [28].…”